Biglycan and Fibromodulin Have Essential Roles in Regulating Chondrogenesis and Extracellular Matrix Turnover in Temporomandibular Joint Osteoarthritis

Abstract

The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn Fmod؊/؊ ). Given the unavailability of cell lines, we first isolated primary MCCs and found that they were phenotypically unique from hyaline articular chondrocytes isolated from the knee joint. Using Bgn Fmod؊/؊ MCCs, we discovered the early basis for temporomandibular joint osteoarthritis arises from abnormal and accelerated chondrogenesis. Transforming growth factor (TGF)-␤1 is a growth factor that is critical for chondrogenesis and binds to both biglycan and fibromodulin. Our studies revealed the sequestration of TGF-␤1 was decreased within the ECM of Bgn ؊/0 Fmod ؊/؊ MCCs, leading to overactive TGF-␤1 signal transduction. Using an explant culture system, we found that overactive TGF-␤1 signals induced chondrogenesis and ECM turnover in this model. We demonstrated for the first time a comprehensive study revealing the importance of the ECM in maintaining the mandibular condylar cartilage integrity and identified biglycan and fibromodulin as novel key players in regulating chondrogenesis and ECM turnover during temoporomandibular joint osteoarthritis pathology.

Deficiency of Biglycan Causes Cardiac Fibroblasts to Differentiate into a Myofibroblast Phenotype

“…In line with the present results myofibroblasts of human epiretinal membranes show increased TGF-␤RII expression (60). Furthermore, bgn and fibromodulin double-deficient mandibular condylar chondrocytes have overactive TGF-␤ signaling leading to chondrogenesis and ECM turn over (17,61). Therefore, the present findings are in line with the literature on SLRPs suggesting that lack of SLRPs may in certain biological context enhance TGF-␤ signaling.…”

Role of Subchondral Bone during Early-stage Experimental TMJ Osteoarthritis

“…, is a well-established genetic model for TMJ OA (Wadhwa et al, 2005a,b;Embree et al, 2010). We have previously reported late-stage osteoarthritic changes in both bgn…”

“…The small leucine-rich repeat proteoglycans (SLRPs) are a family of extracellular matrix proteins highly expressed in both cartilage and bone (Embree et al, 2010). A mouse line doubly deficient in 2 members of the SLRP family, biglycan and fibromodulin (bgn…”

Dentin Sialophosphoprotein (DSPP) Plays an Essential Role in the Postnatal Development and Maintenance of Mouse Mandibular Condylar Cartilage

“…The temporomandibular joint (TMJ) is a unique articulating joint that is essential for proper mastication and verbal communication (Embree et al 2010). The mandibular condyle, whose surfaces are covered by fibrocartilage, is a component of the TMJ and is structurally distinct from both growth plate and articular cartilage in limbs (Serrano et al 2011).…”

“…Chondrocytes reside within the ECM and synthesize and maintain the ECM under normal conditions of low turnover (Goldring and Goldring 2007). The ECM plays a critical role in the preservation of cartilage tissue integrity (Embree et al 2010).…”